Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is epidemic in the United States and other countries and poses a significant health and economic burden. As CA-MRSA is now the predominant MRSA clone in the community and in many healthcare settings, clinicians and infection control practitioners face new challenges. The community is now an important and expanding reservoir for the spread of virulent CA-MRSA strains into hospitals, likely increasing the severity of nosocomial MRSA infections. Existing infection prevention strategies are based on risk factors associated with the transmission of traditional healthcare-associated MRSA strains. To effectively mitigate the spread of contemporary CA- MRSA strains in both healthcare and community settings, we must first understand the transmission dynamics of this epidemic clone, identify factors associated with acquisition and infection, and determine the significance of environmental surface contamination in the spread of the organism. The clustering of CA-MRSA infections in households makes this a logical setting in which to study CA- MRSA transmission dynamics. Our prior studies revealed a high prevalence of MRSA colonization in household contacts of children with MRSA disease and demonstrated that decolonization of all household members resulted in a decreased incidence of skin and soft tissue infection (SSTI) in index patients and household contacts compared to decolonization of the index patient alone. Pediatric patients with CA-MRSA infection and their household members will be recruited to participate in a one-year prospective natural history study of CA-MRSA household transmission dynamics. Commonly handled household objects and surfaces, and pet dogs and cats, will be cultured. Serial colonization status and infection incidence in participants will be ascertained over 12 months. Molecular typing will be performed on all recovered MRSA isolates to illuminate the directionality of transmission and to determine whether infecting strains resemble endogenous colonizing strains, strains recovered from household contacts, or strains recovered from environmental surfaces. Using mixed effects logistic regression modeling, the relationships among risk factors at multiple levels (including household colonization pressure, host behavioral practices, and contamination of household surfaces and pets) will be elucidated to identify factors conferring the greatest risks for CA-MRSA colonization, infection, and transmission. Subsequently, study participants will be randomized into an intervention study to compare the effectiveness of decolonization measures (application of nasal mupirocin and dilute bleach water baths) in preventing recurrent SSTI when these measures are performed by all household members compared to decolonizing only household members with a history of SSTI in the prior year (as determined during the natural history study). Colonization status and infection incidence will be followed for an additional 12 months. These studies will inform optimized interventions to reduce the burden of CA-MRSA colonization and disease. PUBLIC HEALTH RELEVANCE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a significant public health problem. The proposed research will define how these bacteria are transmitted within households, identify risk factors for skin colonization and infection, and evaluate approaches to prevent CA-MRSA infection. Our results will help improve methods to reduce CA-MRSA disease.